Featured Research

from universities, journals, and other organizations

Molecular mechanism for some anti-arrhythmia drugs discovered

Date:
June 15, 2011
Source:
University of British Columbia
Summary:
Researchers -- using an innovative, atom-by-atom substitution method -- have uncovered the mechanism by which a particular class of drugs controls irregular heartbeats.

University of British Columbia researchers -- using an innovative, atom-by-atom substitution method -- have uncovered the mechanism by which a particular class of drugs controls irregular heartbeats.

Related Articles


The findings, published June 14 in the online journal Nature Communications, shed light on why certain anti-arrhythmic drugs (AADs) have dramatically different effects on the heart's behavior compared to others, and why the same drug can be beneficial in some instances and fatal in others. The discovery points the way toward development of better treatments for the condition, which is a leading cause of stroke.

AADs are typically categorized on the basis of their effects on the electrocardiogram (ECG), not on their inherent qualities or molecular mechanisms. Such sorting of drugs, while common in pharmacology, limits our ability to improve upon them, said principal investigator Chris Ahern, an Assistant Professor in the UBC Department of Anesthesiology, Pharmacology and Therapeutics.

"By understanding how these drugs work at the molecular level, we will be better able to pick and choose the traits we want -- and those we don't -- when developing new drugs for this dangerous condition," said Ahern, who is a member of the Life Sciences Institute at UBC and of the Brain Research Centre at UBC and the Vancouver Coastal Health Research Institute.

All three categories of Class 1 AADs, called Class 1a, 1b and 1c, bind to the same site within the cardiac sodium channel, a sophisticated protein that generates electrical impulses to the heart. Ahern, working with postdoctoral fellow Stephan Pless, in the same department, and Jason Galpin and Adam Frankel from the Faculty of Pharmaceutical Sciences, sought to discover whether the differences were due to varying levels of electrostatic interactions between the drugs and the amino acids in the channel.

They created artificial amino acids to mirror the behavior of the cardiac sodium channel, probing the AADs' structure and the contribution of electrical charge -- a technique that follows in the footsteps of UBC Nobel Laureate Michael Smith and has been used successfully by a few labs worldwide. The researchers substituted individual hydrogen atoms with fluorine atoms, which display different electrical characteristics, to see if those modifications affect the AADs' ability to bind to the cardiac sodium channel.

The various alterations of the amino acids were introduced into cells, and the researchers measured the resulting electrical current. They found that each substitution of a hydrogen atom with a fluorine atom lowered the level of AAD binding to the cardiac sodium channel.

"We did this in steps, and observed a clear trend with the Class 1b AADs," said Pless, who has been working at UBC since 2008 on a research fellowship from the Heart & Stroke Foundation of BC & Yukon. "The trend held over each atom replacement, which confirmed that electrostatic reactions are indeed taking place with the drugs. But we found little evidence of the same electrical interaction with 1a and 1c drugs."

The distinction of 1b drugs explains their particular ability to both rapidly change the heart's behaviour, and to rapidly "shut off," Pless said.

"By zeroing in on these molecular actions, drug developers will be better able to isolate the most desirable qualities of each drug -- as well as the most threatening -- to find a more effective, safer version," he said.


Story Source:

The above story is based on materials provided by University of British Columbia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Stephan A. Pless, Jason D. Galpin, Adam Frankel, Christopher A. Ahern. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels. Nature Communications, 2011; 2: 351 DOI: 10.1038/ncomms1351

Cite This Page:

University of British Columbia. "Molecular mechanism for some anti-arrhythmia drugs discovered." ScienceDaily. ScienceDaily, 15 June 2011. <www.sciencedaily.com/releases/2011/06/110614115033.htm>.
University of British Columbia. (2011, June 15). Molecular mechanism for some anti-arrhythmia drugs discovered. ScienceDaily. Retrieved March 30, 2015 from www.sciencedaily.com/releases/2011/06/110614115033.htm
University of British Columbia. "Molecular mechanism for some anti-arrhythmia drugs discovered." ScienceDaily. www.sciencedaily.com/releases/2011/06/110614115033.htm (accessed March 30, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, March 30, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Ebola Lockdown

Sierra Leone in Ebola Lockdown

Reuters - News Video Online (Mar. 27, 2015) Millions of people in Sierra Leone are urged to stay at home in a three-day lockdown to help end the country&apos;s Ebola outbreak. Paul Chapman reports. Video provided by Reuters
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins